1. Field of the Invention
This invention relates to a method for the preparation of a gamma globulin solution suitable for intravenous use, by treating with a peptic enzyme the gamma globulin fraction of a serum obtained in known manner.
2. Description of the Prior Art
Antibody-containing gamma globulin preparations from human plasma are used for intramuscular injections in various pathological conditions. The known preparations, however, have the disadvantage that a sufficient dose for treatment by the intramuscular route leads to considerable pain and about one-third of the administered gamma globulin is broken down before resorption and the greater part is resorbed only slowly.
The discomfort arises not only from the volume of the injection required but also from incompatability reactions.
With intravenous administration of such preparations, very serious secondary reactions are observed in the patient, for example, shivering, rise of temperature, asthma, loss of blood pressure and circulatory disturbances which can indeed even lead to circulatory collapse.
On the other hand, however, the intravenous use of gamma globulin is to be desired, as it presents the only possible alternative in the case of acute illness (such as sepsis) because it is only by this route that the antibodies contained in the gamma globulin can be rapidly and fully effective. It is desirable, however, that the intravenously administered gamma globulin should have a long dwell time in the organism, should not be chemically modified and should be capable of being broken down in the normal way. In addition, the antibacterial, antiviral and antitoxic effect of the gamma globulin should be largely retained. In this way a better utilization of the administered gamma globulin and also a purposeful dosing of the preparation could be achieved.
It is known, in order to prepare a disintegrated gamma globulin which does not influence the complement system, to treat the gamma globulin fraction of the serum which is obtained in known manner, for instance by ammonium sulphate precipitation or alcohol precipitation, at a pH value between 1.5 and 5.5 and a temperature between 0.degree. and 50.degree. C. for two hours to two days with pepsin, for instance with 25,000 to 200,000 E Pepsin per 100 g of protein to be broken down, with continual monitoring of the anti-complementary effect and until the complement-inactivating effect is eliminated, to separate the obtained disintegrated gamma globulin in known manner, for instance by fractionated precipitation with neutral salts or organic solvents or by ultrafiltration of low-molecular separation products, to carry out sterile filtration and, if necessary, to freeze dry.
Other enzymatic processes for the production of a gamma globulin, as described above, are also known, for example by using plasmin.
It is also known that gamma globulins of various origins bind up complement in an uncontrolled and unspecific manner, especially the complement factor C'1 of human and guinea-pig serum. This property is also possessed by the principal fraction of the gamma globulin which is obtained by careful treatment, for example, by preparative electrophoresis or ultracentrifuging or by diethylaminoethyl (DEAE) cellulose filtration or gelfiltration with or without ion exchanger properties.
To summarize it can be established that there are no methods which comply with the initially mentioned requirements of an intravenously applicable gamma globulin.
It is an object of the present invention to produce a gamma globulin suitable for intravenous use, which shall possess all the required, previously mentioned characteristics.